The objective of this research is an in situ study of the cholinergic and adrenergic receptor systems in human erythrocytes. Recent work by the author has shown that erythrocyte response to neurotransmitters resembles smooth muscle contraction in many respects. Investigation of excitation and contraction mechanisms in these simple, discrete, easily manipulated cells may provide findings relevant to function and pathology in experimentally inaccessible cells such as those in vascular and respiratory smooth muscle. The composition, physical disposition, and chemistry of these neurotransmitter receptor systems will be studied in intact cells, using drug binding, crosslinking, fluorescence and electron spin resonance spectroscopy, selective extraction, and partial reconstitution techniques. The physiological consequences of erythrocyte excitation will be studied. The observed response is a decrease in cell deformability. This may have profound systemic effects, since the stress exerted on the walls of small blood vessels by passing cells is an important factor in blood pressure regulation. The pressure required to squeeze cells through narrow vessels will be studied using microcapillary techniques. The effects of neurotransmitters on intracellular properties (metabolism, transport, oxygen binding) will be investigated. Certain hemolytic diseases (hereditary spherocytosis) which arise from specific ion permeability defects will be studied to determine whether neurotransmitter receptors are involved in regulation of cell volume by means of ion fluxes.